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By Derek Vargas, Scientific Affairs, MedGenome Inc
Spatial transcriptomics is a technology that allows the analysis of gene expression patterns within a tissue sample in their spatial context. It enables researchers to obtain a comprehensive and high-resolution view of the transcriptome, the set of all expressed genes, across different regions of the tissue. In traditional transcriptomics, gene expression is measured from homogenized cell populations, which can mask important differences in gene expression between different cell types and regions. Spatial transcriptomics, on the other hand, allows researchers to analyze gene expression patterns in intact tissue sections while retaining their spatial information.
Spatial transcriptomics typically involves the following steps:
- • Preparation of the tissue sample: Tissue sections are cut and placed on a surface that contains oligonucleotide-labeled spots or barcode arrays.
- • Capture of mRNA molecules: The mRNA molecules in the tissue section are captured and attached to the labeled spots, allowing for the spatial location of the mRNA to be retained.
- • High-throughput sequencing: The captured mRNA molecules are amplified and subjected to high-throughput sequencing, generating a large amount of data.
- • Data analysis: The sequencing data is analyzed to identify the expression levels of different genes and their spatial distribution within the tissue section.
Overall, spatial transcriptomics provides a powerful tool for studying complex tissues, such as the brain, where multiple cell types with distinct gene expression profiles are tightly organized in intricate spatial arrangements. The technology can help researchers to gain new insights into the molecular mechanisms of development, disease, and tissue function. There are several platforms available for spatial transcriptomics, however the two most widely used platforms are Visium (10x Genomics) and GeoMx (Nanostring).
Visium Advances Biomarker Discovery
Visium is a spatial transcriptomics technology developed by 10x Genomics that enables high-throughput analysis of gene expression in intact tissue sections. Visium builds on the principle of spatial transcriptomics and allows for the analysis of the whole transcriptome in a spatially resolved manner, meaning that researchers can obtain detailed information on the gene expression patterns within a tissue sample while maintaining their spatial context.
The Visium platform is based on the capture of mRNA molecules on an array of polymeric spots on a glass slide. The captured mRNA molecules are then barcoded, reverse transcribed, and amplified. The amplified cDNA is sequenced using high-throughput sequencing technologies, generating millions of reads that are aligned to a reference genome. The resulting data can be visualized and analyzed using various software tools provided by 10x Genomics or other bioinformatics platforms. The technology can be used to study complex tissues and biological processes, such as development, disease, and tumor microenvironments, by providing information on the expression levels of thousands of genes in each region of the tissue section.
Nanostring GeoMx Allows Targeted Analysis of Spatial Transcriptome
NanoString’s GeoMx is another spatial profiling technology that enables the analysis of gene expression at high resolution within a tissue sample while retaining its spatial context. The technology is based on the digital barcoding and imaging of RNA molecules in situ, allowing for the precise spatial localization of gene expression patterns within a tissue sample. The GeoMx system utilizes a set of molecular probes that are pre-designed or customized for specific gene targets. The probes are attached to a surface and hybridized to the RNA molecules in the tissue sample, creating a unique barcode sequence for each molecule. The barcoded RNA molecules are then imaged using a high-resolution imaging system, enabling the precise spatial localization of gene expression patterns in the tissue.
The GeoMx technology can be used to analyze hundreds to thousands of genes simultaneously, allowing researchers to gain a comprehensive view of the transcriptome across different regions of the tissue. The technology can be used to study various biological questions, such as the identification of cell types, the characterization of disease-associated gene expression patterns, and the discovery of new biomarkers for diagnosis and therapy. The GeoMx system is also compatible with other NanoString technologies, such as the nCounter platform, enabling researchers to combine spatial profiling with digital quantification of gene expression in the same sample. The technology has applications in various fields, including oncology, immunology, and neuroscience, and can be used in both research and clinical settings.
Conclusion
Visium and GeoMx are both spatial profiling technologies, but there are some key differences between the two platforms. Visium doesn’t require any large lab equipment. The chemistry takes place on a special microscope slide and the workflow can be completed with standard lab equipment found in many cell biology labs. On the other hand, GeoMx does require special machinery, which can make it more difficult for smaller labs to utilize this technology. Another major difference is that Visium takes an unbiased approach to spatially profiling tissues; any tissue placed in the capture area of the slide will be sequenced. GeoMx requires some prior knowledge of the tissue since regions of interest must be chosen. This difference makes Visium a great tool for discovery research, while GeoMx is great for clinical research.
Overall, both Visium and GeoMx are powerful tools for studying gene expression patterns and cellular heterogeneity within complex tissues. The choice of platform depends on the research question and the specific needs of the experiment, as each platform has its own strengths and limitations. Currently, MedGenome is offering full bioinformatics services related to Visium datasets. There are many standard and custom analysis options available to accommodate most projects. Additionally, our genomics lab is in the process of adopting spatial transcriptomics technologies. We expect end-to-end Visium spatial profiling services to be offered in the near future.
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